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Purpose of Review: Parkinson disease dementia (PDD) is a multisystem disorder involving motor and nonmotor symptoms. Therapeutic options for management of cognitive and neuropsychiatric symptoms are relatively limited when compared to motor symptoms and have been an active area of study. We present the reader with a critical appraisal of evidence for approved and recently investigated therapies in the management of PDD, particularly highlighting recent findings in the management of cognitive impairment and psychotic symptoms. Recent Findings.: Several disappointing trials for treatment of cognitive impairment in PDD leave rivastigmine as the only on-label treatment option; evidence supporting possible benefit of other therapies is reviewed. Several clinical trials are currently ongoing and studying novel treatment options for cognitive impairment in PDD. Pimavanserin has demonstrated efficacy for management of Parkinson disease psychosis. In a randomized clinical trial, integrated outpatient palliative care, in addition to standard care, improved multiple aspects of care in this patient population compared to standard care alone. Summary: Rivastigmine, in particular transdermal administration due to greater tolerability, has the best evidence for treatment of cognitive impairment in PDD. Evidence for other acetylcholinesterase inhibitors and memantine is mostly supportive but less conclusive. Research is ongoing to overcome this unmet need for treatment options for cognitive symptoms of PDD. Psychotic symptoms of PDD are best managed with pimavanserin, which was recently investigated and approved in the USA. Caution is needed in prescribing practices, including treatment of motor symptoms, to avoid iatrogenic worsening of nonmotor symptoms.Palliative care should be integrated into the management of PDD. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics are used in Parkinson disease (PD) to treat psychosis, mood, and behavioral disturbances. Commonly used antipsychotics differ substantially in their potential to worsen motor symptoms through dopaminergic receptor blockade. Recent real-world data on the use and continuation of antipsychotic therapy in PD are lacking. The objectives of this study are to (1) examine the continuation of overall and initial antipsychotic therapy in individuals with PD and (2) determine whether continuation varies by drug dopamine receptor blocking activity.Methods: We conducted a retrospective cohort study using U.S. commercially insured individuals in Optum 2001-2019. Adults aged 40 years or older with PD initiating antipsychotic therapy, with continuous insurance coverage for at least 6 months following drug initiation, were included. Exposure to pimavanserin, quetiapine, clozapine, aripiprazole, risperidone, or olanzapine was identified based on pharmacy claims. Six-month continuation of overall and initial antipsychotic therapy was estimated by time to complete discontinuation or switching to a different antipsychotic. Cox proportional hazards models evaluated factors associated with discontinuation.Results: Overall, 38.6% of 3566 PD patients in our sample discontinued antipsychotic therapy after the first prescription, 61.4% continued with overall treatment within 6 months of initiation. Clozapine use was too rare to include in statistical analyses. Overall therapy discontinuation was more likely for those who initiated medications with known dopamine-receptor blocking activity (adjusted hazard ratios 1.76 [95% confidence interval 1.40-2.20] for quetiapine, 2.15 [1.61-2.86] for aripiprazole, 2.12 [1.66-2.72] for risperidone, and 2.07 [1.60-2.67] for olanzapine), compared with serotonin receptor-specific pimavanserin. Initial antipsychotic therapy discontinuation also associated with greater dopamine-receptor blocking activity medication use - adjusted hazard ratios 1.57 (1.28-1.94), 1.88 (1.43-2.46), 2.00 (1.59-2.52) and 2.03 (1.60-2.58) for quetiapine, aripiprazole, risperidone, and olanzapine, respectively, compared with pimavanserin. Similar results were observed in sensitivity analyses.Conclusions: Over one-third of individuals with PD discontinued antipsychotic therapy, especially if the initial drug has greater dopamine-receptor blocking activity. Understanding the drivers of antipsychotic discontinuation, including ineffectiveness, potentially inappropriate use, clinician inertia, patient adherence and adverse effects, is needed to inform clinical management of psychosis in PD and appropriate antipsychotic use in this population. [ABSTRACT FROM AUTHOR]